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Synthesis of Isonucleoside-Incorporated Oligonucleotides and Their Binding Abilities with Complementary Sequences
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作者 史继峰 王占黎 +1 位作者 张亮仁 张礼和 《Journal of Chinese Pharmaceutical Sciences》 CAS 2004年第1期4-9,共6页
Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was in... Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was investigated by thermal denaturation studies. Results Fourkinds of single isonucleoside containing oligonucleotides were synthesized. The results of thermaldenaturation showed that the existence of isonucleoside decreased the stability of duplex, and theeffect was more obvious when the isonucleoside was in the middle of the sequence. No obviousdifference was observed when 6'-OH of isonucleoside was free or was protected by allyl group.Conclusions The existence of isonucleoside in oli-gonucleotide makes chain twist and decreased thestability of duplex. 展开更多
关键词 isonucleoside nucleotides HYBRIDIZATION thermal denaturation
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Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients 被引量:4
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作者 Xia Zhu Kang Chao +7 位作者 Miao Li Wen Xie Hong Zheng Jin-Xin Zhang Pin-Jin Hu Min Huang Xiang Gao Xue-Ding Wang 《World Journal of Gastroenterology》 SCIE CAS 2019年第38期5850-5861,共12页
BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants signif... BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended. 展开更多
关键词 Crohn’s disease Thioguanine nucleotidE levels nucleoside diphosphatelinked MOIETY X-type MOTIF 15 Thiopurine-induced LEUKOPENIA
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Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study
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作者 Huimin Yin Xianqiang Wang +6 位作者 Shouhua Zhang Shaohua He Wenli Zhang Hongting Lu Yizhen Wang Jing He Chunlei Zhou 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2024年第3期298-305,共8页
Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to ev... Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings. 展开更多
关键词 nucleotide excision repair POLYMORPHISMS HEPATOBLASTOMA SUSCEPTIBILITY
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Nucleotide Contribution to the Functioning of SERT, Na /K ATPase and GPCR Proteins
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作者 Wynford Robert Williams 《Journal of Biosciences and Medicines》 2024年第5期61-76,共16页
Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase an... Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (SERT), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating SERT and N/K ATPase receptors. Minimum energy conformers of SERT antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a SERT-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes. 展开更多
关键词 SERT SSRI GPCR Sodium/Potassium ATPase nucleotides Depression
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Metformin promotes anti-tumor immunity in STK11 mutant NSCLC through AXIN1-dependent upregulation of multiple nucleotide metabolites
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作者 ZHIGUO WANG KUNLIN LI +12 位作者 CONGHUA LU MINGXIA FENG CAIYU LIN GUOFANG YIN DAN LUO WENYI LIU KAIYU JIN YUANYAO DOU DI WU JIE ZHENG KEJUN ZHANG LI LI XIANMING FAN 《Oncology Research》 SCIE 2024年第10期1637-1648,共12页
Background:Metformin has pleiotropic effects beyond glucose reduction,including tumor inhibition and immune regulation.It enhanced the anti-tumor effects of programmed cell death protein 1(PD-1)inhibitors in serine/th... Background:Metformin has pleiotropic effects beyond glucose reduction,including tumor inhibition and immune regulation.It enhanced the anti-tumor effects of programmed cell death protein 1(PD-1)inhibitors in serine/threonine kinase 11(STK11)mutant non-small cell lung cancer(NSCLC)through an axis inhibition protein 1(AXIN1)-dependent manner.However,the alterations of tumor metabolism and metabolites upon metformin administration remain unclear.Methods:We performed untargeted metabolomics using liquid chromatography(LC)-mass spectrometry(MS)/MS system and conducted cell experiments to verify the results of bioinformatics analysis.Results:According to the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database,most metabolites were annotated into metabolism,including nucleotide metabolism.Next,the differentially expressed metabolites in H460(refers to H460 cells),H460_met(refers to metformin-treated H460 cells),and H460_KO_met(refers to metformin-treated Axin1-/-H460 cells)were distributed into six clusters based on expression patterns.The clusters with a reversed expression pattern upon metformin treatment were selected for further analysis.We screened out metabolic pathways through KEGG pathway enrichment analysis and found that multiple nucleotide metabolites enriched in this pathway were upregulated.Furthermore,these metabolites enhanced the cytotoxicity of activated T cells on H460 cells in vitro and can activate the stimulator of the interferon genes(STING)pathway independently of AXIN1.Conclusion:Relying on AXIN1,metformin upregulated multiple nucleotide metabolites which promoted STING signaling and the killing of activated T cells in STK11 mutant NSCLC,indicating a potential immunotherapeutic strategy for STK11 mutant NSCLC. 展开更多
关键词 METFORMIN Serine/threonine kinase 11(STK11) Lung cancer Axis inhibition protein 1(AXIN1) nucleotide metabolites
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The Nucleosides Contents and Their Variation in Natural Cordyceps sinensis and Cultured Cordyceps Mycelia 被引量:15
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作者 李绍平 李萍 +3 位作者 季晖 朱荃 董婷霞 詹华强 《Journal of Chinese Pharmaceutical Sciences》 CAS 2001年第4期175-179,共5页
Aim: To compare the contents of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia, and to study the effect of humidity and heat on the content of nucleosides. Methods: The contents of nucleos... Aim: To compare the contents of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia, and to study the effect of humidity and heat on the content of nucleosides. Methods: The contents of nucleosides were determined by using high performance capillary electrophoresis (HPCE). Beckman P/ACE System 5010 apparatus equipped with a UV detector and a Beckman untreated fused-silica capillary (57 cm 75 mm, 50 cm effective length) was used. Before sample injection, the capillary was rinsed with 1 molL-1 sodium hydroxide solution and running buffer for 5 min, respectively. A voltage of 20 kV was applied for the separation. Pressure injection was 586 kPa for 6 seconds, and the wavelength of detector was 254 nm. The running time was 20 min at 20 oC. The effect of humidity and heat on the contents of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia was observed for 1, 3, 5 and 10 days at temperature 40 oC, and relative humidity 75%. Results: The content of nucleosides from natural Cordyceps sinensis was higher than that from cultured Cordyceps mycelia. But the contents of nucleosides from freshly collected natural Cordyceps sinensis were very low, even below the limit of quantitation. The contents of nucleosides from natural Cordyceps sinensis were significantly increased by humidity and heat, but this phenomenon was not observed in cultured Cordyceps mycelia. Conclusion: There are differences between the nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia. The nucleosides in natural Cordyceps sinensis may be derived from the degradation of nucleic acids. This implies that adenosine being used for the quality control of natural Cordyceps sinensis may have to be reconsidered. 展开更多
关键词 CORDYCEPS nucleosideS ADENOSINE GUANOSINE URIDINE
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Separation of Nucleotides in Swine Tissues Using Capillary Zone Electrophoresis
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作者 顾峻岭 刘玉 +2 位作者 傅若农 鲁红军 张燕婉 《Journal of Beijing Institute of Technology》 EI CAS 1994年第2期155-161,共7页
Capillary zone electrophoresis has been applied to the analysis of nucleotides. The effects of buffer concentration. pH and other operating conditions on the separation were investigated and optimized. By using the me... Capillary zone electrophoresis has been applied to the analysis of nucleotides. The effects of buffer concentration. pH and other operating conditions on the separation were investigated and optimized. By using the method, separation and identification of nuclotides in swine tissues were completed. 展开更多
关键词 SEPARATION nucleotides/capillary zone electrophoresis
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Simultaneous determination of five nucleosides and nucleobases in Panax notoginseng using high-performance liquid chromatography 被引量:1
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作者 王静 王一涛 李绍平 《Journal of Chinese Pharmaceutical Sciences》 CAS 2007年第2期79-83,共5页
Aim To quantitatively determine five nucleosides and nucleobases, including cytidine, uridine, guanosine, adenosine and uracil in different parts of Panax notoginseng. Methods Separation was performed on a Zorbax SB-A... Aim To quantitatively determine five nucleosides and nucleobases, including cytidine, uridine, guanosine, adenosine and uracil in different parts of Panax notoginseng. Methods Separation was performed on a Zorbax SB-Aq column using a gradient elution with mobile phase of 8 mmol^L-1 ammonium acetate aqueous solution (A) and methanol (B). The assay was carried out at a flow rate of 1 mL·min^-1 at 25 ℃ with the diode-array detection at 260 nm. Results Cytidine, uridine, guanosine, adenosine and uracil had good linearity in the ranges of 1.79 - 57.40 μg·mL^-1 (r^2 = 1.0000), 3.30 - 105.60 μg·mL^-1 (r^2 = 1.0000), 3.09 - 98.80 μg·mL^ -1(r^2 = 0.9999), 2.77 - 88.60 μg·mL^-1 (r^2 = 1.0000) and 0.38 - 12.30 μg·mL ^-1 (r^2 = 1.0000) with average recoveries of 93.9%, 96.5%, 92.7%, 93.2% and 98.8%, respectively. The content of cytidine, uridine, guanosine, adenosine and uracil in different parts of P. notogingeng were significantly different. Conclusion This is the first report on quantitative determination of nucleosides and nucleobases in P notoginseng. 展开更多
关键词 Panax notoginseng nucleoside NUCLEOBASE High-performance liquid chromatography (HPLC)
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Clinical outcomes of cessation of nucleoside/nucleotide analogues in Chinese patients with HBeAg-negative chronic hepatitis B
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作者 Fengyi Li Yadong Zhang +3 位作者 Chao Liu Juan Li Dali Zhang Yinjie Gao 《iLIVER》 2024年第2期22-27,共6页
Background and aims:Cessation of nucleoside/nucleotide analogue(Nuc)therapy in patients with HBeAg-negative chronic hepatitis B(CHB)remains controversial.Methods:In this prospective,single-center cohort study,we recru... Background and aims:Cessation of nucleoside/nucleotide analogue(Nuc)therapy in patients with HBeAg-negative chronic hepatitis B(CHB)remains controversial.Methods:In this prospective,single-center cohort study,we recruited 45 patients with HBeAg-negative CHB from The Fifth Medical Center of Chinese People's Liberation Army General Hospital in China's Mainland.Patients were classified into a Nuc cessation group(n?27)and Nuc continuation group(n?18)and followed-up for 36 months.Nuc were stopped after being inactive for at least 4 years(normal alanine aminotransferase(ALT),undetectable hepatitis B virus(HBV)DNA),with liver fibrosisStage1(S1)and inflammationGrade(G1).Results:Within 3 years of follow-up,51.9%patients with Nuc cessation had virological relapse and 14.8%had ALT elevation,while all patients with Nuc continuation had undetectable HBV DNA and normal ALT.The rate of HBsAg loss after Nuc cessation was 22.2%compared with no seroconversion in patients with Nuc continuation.The hepatitis flare rate was 11.1%and there were no cases of hepatic decompensation after Nuc cessation.End of treatment(EOT)HBsAg,HBV RNA,and decline in HBV core-related antigen(HBcrAg)rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation.Conclusion:This study showed favorable HBsAg loss and low hepatitis flare rates after Nuc cessation.EOT HBsAg,HBV RNA,and decline in HBcrAg rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation. 展开更多
关键词 nucleoside analogues nucleotide analogues Therapy cessation HBeAg-negative Clinical relapse
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Viral infection parameters not nucleoside analogue itself correlates with host immunity in nucleoside analogue therapy for chronic hepatitis B 被引量:16
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作者 Cheng-Zhong Li Jing-Jing Hu +5 位作者 Jian-Ya Xue Wei Yin Ya-Yun Liu Wen-Han Fan Hao Xu Xue-Song Liang 《World Journal of Gastroenterology》 SCIE CAS 2014年第28期9486-9496,共11页
AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
关键词 Chronic hepatitis B nucleoside analogues Immune modulation Programmed death-1 CD4+CD25+FoxP3+T regulatory cells
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Application of nucleoside analogues to liver transplant recipients with hepatitis B 被引量:3
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作者 Zhuo-Lun Song Yu-Jun Cui +2 位作者 Wei-Ping Zheng Da-Hong Teng Hong Zheng 《World Journal of Gastroenterology》 SCIE CAS 2015年第42期12091-12100,共10页
Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donor... Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts. 展开更多
关键词 nucleoside ANALOGUES LIVER TRANSPLANTATION Hepatit
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Purine nucleotides and their metabolites in patients with type 1 and 2 diabetes mellitus 被引量:2
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作者 Wioleta Dudzinska 《Journal of Biomedical Science and Engineering》 2014年第1期38-44,共7页
We measured the erythrocyte levels of principal nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP), nucleosides (Ado, Guo, Ino) and Hyp with HPLC. Purine concentrations were determined in the erythrocytes of 36 type 1 an... We measured the erythrocyte levels of principal nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP), nucleosides (Ado, Guo, Ino) and Hyp with HPLC. Purine concentrations were determined in the erythrocytes of 36 type 1 and 40 type 2 diabetic patients. The increased dephosphorylation of adenine and guanine nucleotides, indicated by increased Ado, Ino, Guo and Hyp concentrations as the products of purine nucleotide degradation, suggests serious energy metabolism disruptions in diabetes. An increase in AMP, GMP, IMP concentrations, as well as a decrease in AEC and GEC values, points to significant alterations in erythrocyte purine nucleotide concentration. 展开更多
关键词 PURINE nucleotides nucleosideS PURINE BASES Diabetes
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Response to an Escherichia coli K88 oral challenge and productivity of weanling pigs receiving a dietary nucleotides supplement 被引量:3
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作者 Hanlin Li Pinyao Zhao +2 位作者 Yan Lei Tianshui Li InHo Kim 《Journal of Animal Science and Biotechnology》 CAS CSCD 2016年第1期86-94,共9页
Background: Dietary nucleotides, considered as antibiotics alternative, were shown to have positive effects on intestinal hyperaemia, systemic immunity, small-intestinal growth, and hepatic composition in pigs. Howev... Background: Dietary nucleotides, considered as antibiotics alternative, were shown to have positive effects on intestinal hyperaemia, systemic immunity, small-intestinal growth, and hepatic composition in pigs. However, there is no previous research on nucleotide supplementation in weanling pigs under an oral challenged E. coil K88. Therefore, 2 experiments were conducted to investigate the effects of dietary nucleotides on weanling pig growth performance, nutrient digestibility, fecal score, and blood profile after being orally challenged with E. coli K88. Methods: In Exp. 1, a total of 140 weanling pigs [8.33 ± 0.33 kg of body weight (BW), 28-d old] were used in this 42-d feeding trial. Pigs were distributed into 1 of 4 treatments, 5 pigs/pen (3 barrows and 2 gilts) and 7 pens/treatment. Treatments were a control basal diet (CON) or the CON supplemented with 150 (R150), 220 (R220), or 275 (R275) mg/kg to give the three treatment diets. In Exp. 2, 28 weanling pigs (BW = 8.40 ± 0.22 kg, 28-d old) were distributed into 1 of 4 treatments to give 1 pig/pen and 7 pens/treatment in a 42-d feeding and challenge trial. Dietary treatments were the same as in Exp. 1. 0n d 14, all those pigs (BW= 13.3±0.15 kg, 42-d old) were orally dosed with 1.5 mL suspension containing 10 cfu/mL of E. coli K88. Twenty four hours after challenge, blood and excreta samples were collected from each pigs for analysis. Fecal scores were measured on d 7, 14, 21, and 28 of the study. Results: In Exp. 1, overall BW, average daily gain (ADG), gain/feed (G/F) ratio, and nutrient digestibilities were lower (P 〈 0.05) in CON group compared with the nucleotides fed pigs. In Exp. 2, after challenge, IgA, IgM, and IGF-I were higher (P〈 0.05) in the nucleotide groups compared with CON. However, the nucleotide groups had lower (P 〈 0.05) cortisol and TNF-o compared with CON. Fecal E. coil counts and fecal score for the nucleotide groups were lower (P 〈 0.05) than for CON. Conclusions: In conclusion, dietary nucleotides supplementation could improve growth performance, nutrient digestibility, immune status, microbial balance, reduce diarrhea, and provide protection against enterotoxigenic E. coli K88 infection in weanling pigs. 展开更多
关键词 Dietary nucleotides Escherichia coli K88 challenge Growth performance IMMUNITY Nutrientdigestibility Weanling pigs
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Individual and Combined Effects of Nucleotides and Human Milk Oligosaccharides on Proliferation, Apoptosis and Necrosis in a Human Fetal Intestinal Cell Line 被引量:3
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作者 Shelly N. Hester Sharon M. Donovan 《Food and Nutrition Sciences》 2012年第11期1567-1576,共10页
Nucleotides (NT) and human milk oligosaccharides (HMO) individually affect epithelial cell growth, but their combined effects had not been studied. Herein, the impact of NT and HMO on cell proliferation, apoptosis, ne... Nucleotides (NT) and human milk oligosaccharides (HMO) individually affect epithelial cell growth, but their combined effects had not been studied. Herein, the impact of NT and HMO on cell proliferation, apoptosis, necrosis and cell cycle in the fetal epithelial cell line (FHs-74 Int) was determined. Cells were incubated with media containing 2.5% FBS and no epidermal growth factor (Control);fucosyllactose (FL) mix [85% 2’FL/15% 3’FL], sialyllactose (SL) mix [40% 6’SL/10% 3’SL/50% sialic acid (SA)] or LNnT at 125, 250, 500 or 1000 μg/mL with and without 250 μg/mL NT (43% CMP, 18.5% UMP, 16.4% AMP, and 22.0% GMP) for 24 or 72 h. NT alone significantly increased proliferation, but did not affect cell cycle or apoptosis/necrosis. All HMO treatments at 1000 μg/mL significantly decreased proliferation and some were also inhibitory at 250 or 500 μg/mL. When NT and HMO were simultaneously added, NT ameliorated the anti-proliferative effect of HMO. FL significantly increased cells in S phase and SL and LNnT treatments significantly increased cells in G2/M and S phases, which concomitantly decreased cells in G0/G1. HMO with NT significantly decreased the percent of cells in the G2/M phase compared to HMO alone. Higher HMO doses significantly increased the percentage of apoptotic and necrotic cells compared to control. In conclusion, HMO reduced cell proliferation and this effect is partially ameliorated by NT. It appears that HMO initially induced apoptosis/necrosis, which was later evidenced by G2/M cell cycle arrest and decreased proliferation. 展开更多
关键词 Epithelial Cells HUMAN Milk OLIGOSACCHARIDES nucleotides INTESTINE PROLIFERATION
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Effects of Bases on the Stabilities of Nucleoside C4'Radicals 被引量:1
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作者 Bo Lin LIN, Yao FU, Lei LIU, Qing Xiang GUO Department of Chemistry, University of Science and Technology of China, Hefei 230026 《Chinese Chemical Letters》 SCIE CAS CSCD 2003年第10期1073-1076,共4页
C4'-H bond dissociation enthalpies of nucleosides were predicted using theoretical methods to a precision of 1-2 Kcal/mol. It was found that the stability of the C4' nucleoside radical is slightly dependent on... C4'-H bond dissociation enthalpies of nucleosides were predicted using theoretical methods to a precision of 1-2 Kcal/mol. It was found that the stability of the C4' nucleoside radical is slightly dependent on the base. The orders of stability are dA < dG < dT < dC for deoxynucleosides and U < G < A = C for nucleosides. 展开更多
关键词 nucleoside homolysis bond energy DNA lesion substituent effect.
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Design, synthesis and in vitro evaluation of L-amino acid esters prodrugs of acyclic nucleoside phosphonates as anti-HBV agent 被引量:1
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作者 Xiao Zhong Fu Sai Hong Jiang +2 位作者 Jian Xin Yu She Yang RU Yun Ji 《Chinese Chemical Letters》 SCIE CAS CSCD 2007年第7期817-819,共3页
A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity an... A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively. 展开更多
关键词 Acyclic nucleoside phosphonates L-Amino acid PRODRUG Anti-HBV activity
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An efficient and green preparation of 5-aminophosphonate substituted pyrimidine nucleosides under solvent-free conditions 被引量:1
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作者 Xin Ying Zhang Ying Ying Qu Xue Sen Fan 《Chinese Chemical Letters》 SCIE CAS CSCD 2010年第10期1191-1194,共4页
An environmentally benign and highly efficient one-pot preparation of α-aminophosphonates under solvent-free conditions was developed. By employing this method, 5-aminophosphonate substituted pyrimidine nucleosides w... An environmentally benign and highly efficient one-pot preparation of α-aminophosphonates under solvent-free conditions was developed. By employing this method, 5-aminophosphonate substituted pyrimidine nucleosides were synthesized in good to excellent yields starting from 5-forrnyl-2'-deoxyuridine, aniline and dimethylphosphite. 展开更多
关键词 AMINOPHOSPHONATE 5-Substituted pyrimidine nucleoside Solvent-free reaction Green synthesis
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Current prodrug strategies for improving oral absorption of nucleoside analogues 被引量:3
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作者 Youxi Zhang Yikun Gao +1 位作者 Xiaojing Wen Haiying Ma 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2014年第2期65-74,共10页
Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bi... Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues. 展开更多
关键词 nucleoside analogues Oral bioavailability PRODRUG
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Induction of nucleoside phosphorylase in Enterobacter aerogenes and enzymatic synthesis of adenine arabinoside 被引量:5
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作者 Xiao-kun WEI Qing-bao DING +3 位作者 Lu ZHANG Yong-li GUO Lin OU Chang-lu WANG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第7期520-526,共7页
Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5′-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP cou... Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5′-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP could distinctly increase the activities of purine nucleoside phosphorylase (PNPase), uridine phosphorylase (UPase) and thymidine phosphorylase (TPase) when they were added into medium from 0 to 8 h. In the process of enzymatic synthesis of adenine arabinoside from adenine and uracil arabinoside with wet cells of Enterobacter aerogenes DGO-04 induced by cytidine or CMP, the reaction time could be shortened from 36 to 6 h. After enzymatic reaction the activity of NPase in the cells induced remained higher than that in the cells uninduced. 展开更多
关键词 nucleoside phosphorylase (NPase) Enterobacter aerogenes CYTIDINE Cytidine 5'-monophosphate (CMP) Adenine arabinoside
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Synthesis and X-Ray Structure of New Anticancer Nucleosides Based on 1-((2-Hydroxyethoxy)methyl)-5-(phenylthio)-1H-1,2,4-triazole-3-carboxamide 被引量:1
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作者 Yulong Lei Dehua Zhang +2 位作者 Yang Liu Guanghui Tian Hongguang Ge 《Journal of Crystallization Process and Technology》 2014年第3期135-139,共5页
A pair of new anticancer nucleosides based on 1,2,4-triazole nucleosides and 1-((2-hydroxyethoxy) methyl)-5-(phenylthio)-1H-1,2,4-triazole-3-carboxamide have been synthesized, and have given the corresponding products... A pair of new anticancer nucleosides based on 1,2,4-triazole nucleosides and 1-((2-hydroxyethoxy) methyl)-5-(phenylthio)-1H-1,2,4-triazole-3-carboxamide have been synthesized, and have given the corresponding products in excellent yields. Its structures and conformations were confirmed by single crystal X-ray diffraction. 展开更多
关键词 ANTICANCER nucleosideS TRIAZOLE nucleosideS Excellent YIELDS
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